Abstract
Genes for familial hemiplegic migraine (FHM) and episodic ataxia type-2 (EA-2) have been mapped to chromosome 19p13. We characterized a brain-specific P/Q-type Ca2+ channel alpha1-subunit gene, CACNL1A4, covering 300 kb with 47 exons. Sequencing of all exons and their surroundings revealed polymorphic variations, including a (CA)n-repeat (D19S1150), a (CAG)n-repeat in the 3'-UTR, and different types of deleterious mutations in FHM and EA-2. In FHM, we found four different missense mutations in conserved functional domains. One mutation has occurred on two different haplotypes in unrelated FHM families. In EA-2, we found two mutations disrupting the reading frame. Thus, FHM and EA-2 can be considered as allelic channelopathies. A similar etiology may be involved in common types of migraine.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Base Sequence
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Calcium Channels / chemistry
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Calcium Channels / genetics*
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Cerebellar Ataxia / genetics*
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Cerebellar Ataxia / physiopathology
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Chromosome Mapping
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Chromosomes, Human, Pair 19 / genetics
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Cortical Spreading Depression / genetics
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DNA Mutational Analysis
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Female
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Hemiplegia / etiology*
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Humans
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Male
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Migraine Disorders / classification
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Migraine Disorders / complications
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Migraine Disorders / genetics*
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Migraine Disorders / physiopathology
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Models, Molecular
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Molecular Sequence Data
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / genetics*
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Pedigree
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Point Mutation
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Polymorphism, Single-Stranded Conformational
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Sequence Deletion
Substances
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Calcium Channels
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Nerve Tissue Proteins
Associated data
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GENBANK/X99897
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GENBANK/Z80114
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GENBANK/Z80115